Catalytic Metalloporphyrin Protects Against Paraquat Neurotoxicity in vivo

• Published in: Biomedical and environmental sciences 2008-06, Vol.21 (3), p.233-238
• Main Authors: CHEN, Ping, CHEN, Zhen, LI, Ang, LOU, Xiao-Chu, WU, Xiao-Kang, ZHAO, Chun-Jun, WANG, Shi-Long, LIANG, Li-Ping
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - therapeutic use; Antiparkinson Agents - therapeutic use; Behavior, Animal - drug effects; Catalysis; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Dopamine - metabolism; Dopamine transporter; Male; Malondialdehyde - metabolism; Metalloporphyrins - therapeutic use; Mice; Mice, Inbred C57BL; Neuroprotection; Neuroprotective Agents - therapeutic use; Paraquat; Parkinson Disease - drug therapy; Parkinson Disease - metabolism; Parkinson Disease - physiopathology; Parkinson's disease; Substantia Nigra - drug effects; Substantia Nigra - enzymology; Superoxide dismutase mimetics; Tyrosine 3-Monooxygenase - metabolism; 接触反应; 百草枯; 金属卟啉; 除草剂
• ISSN: 0895-3988; 2214-0190
• DOI: 10.1016/S0895-3988(08)60035-5

Objective To examine the neuroprotective effects of a novel manganese porphyrin, manganese （Ill） meso-tetrakis （N,N＇-diethylimidazolium-2-yl） porphyrin （MnTDM）, in the mouse model of Parkinson＇s disease （PD） induced by paraquat （PQ）. Methods Male C57BL / 6 mice were subcutaneously injected with either saline or PQ at 2-day intervals for a total of 10 doses, MnTDM was subcutaneously injected with the PQ 2 h before treatment. Performance on the pole and swim test were measured 7 days after the last injection and animals were sacrificed one day later. Levels of dopamine （DA） and its metabolites in the striatum were measured by high-performance liquid chromatography with an electrochemical detector （HPLC-ECD）. Thiobarbituric acid （TBA） method was used to assay the lipid peroxidation product, malondialdehyde （MDA）, and the number of tyrosine hydroxylase （TH） positive neurons was estimated using immunohistochemistry. Results Pretreatment with MnTI）M significantly attenuated PQ-impaired behavioral performance, depleted dopamine content in striata, increased MDA, and dopaminergic neuron loss in the substantia nigra. Conclusions Oxidative stress plays an important role in PQ-induced neurotoxicity which can be potentially prevented by manganese porphyrin. These findings also propose a possible therapeutical strategy for neurodegenerative disorders associated with oxidative stress such as PD.